This pilot clinical trial studies cyclodextrin-based nanopharmaceutical CRLX101 in treating patients with advanced or metastatic stomach, gastroesophageal, or esophageal cancer that has progressed through at least one prior regimen of chemotherapy and cannot be removed by surgery. CRLX101 delivers the cytotoxic topoisomerase-1 inhibitor camptothecin into tumor cells and is hypothesized to interrupt the growth of tumor cells.

Patients receive cyclodextrin-based polymer-camptothecin CRLX101 IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the completion of 6 courses, patients achieving stable disease or better may receive treatment for an additional 6 months.

Patients receive cyclodextrin-based polymer-camptothecin CRLX101 intravenously (IV) over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients must have received at least one prior chemotherapy regimen for their unresectable or metastatic disease, not including treatment administered in the adjuvant and/or neoadjuvant setting for curative intent

Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

Subjects with a life expectancy >= 12 weeks

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately and be discontinued on study; subjects should be instructed to notify the investigator if it is determined after completion of the study that they became pregnant during the treatment phase of the study; the anticipated date or birth or termination of the pregnancy should be provided at the time of the initial report; whenever possible, a pregnancy should be followed to term, any premature terminations reported, and the status of the mother and the child should be reported to the study monitor after delivery; if the outcome of the pregnancy meets any severe adverse events (SAE) classification criterion, the investigator must follow the procedures for reporting SAEs; any neonatal death occurring =< 30 days after birth must also be reported as a SAE

Subjects must have an electrocardiogram without evidence of clinically significant conduction abnormalities or active ischemia as determined by the investigator and an acceptable QTc interval

All subjects must have the ability to understand and the willingness to sign a written informed consent

Subjects must not have received prior chemotherapy or radiation within < 4 weeks prior to first dose of study drug

Subjects may be entered if they have received prior radiation therapy involving =< 30% of the bone marrow; any prior radiation therapy must have been administered >= 4 weeks prior to first dose of study drug and the subject must be recovered from the acute toxic effects of the treatment prior to first dose of study drug (defined as a return to baseline or a severity of =< grade 1)

Subjects may be enrolled with a history of treated brain metastases that are clinically stable for >= 4 weeks prior to the first dose of study drug; subjects may not be currently receiving dexamethasone

Exclusion Criteria:

Female subjects who are pregnant or nursing

Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study drug or those who have not had adverse events return to baseline severity level or a severity of grade 1 due to agents administered more than 4 weeks prior to first dose of study drug

Subjects with a history of congestive heart failure (CHF) requiring medical therapy

History of prior malignancy not cured by excision; patients with non-melanoma skin cancer or carcinoma in situ of the cervix are not excluded, but patients with other prior malignancies must have had at least 2-year disease free interval

Concurrent therapeutic anticoagulation: PTT less than or equal to 1.5 x ULN or low dose aspirin and low-molecular weight heparin only are allowed; Coumadin will be allowed on a case by case basis if use is chronic and approved by the study medical monitors

Any major surgery =< 4 week prior to first dose of study drug

Concurrent use of filgrastim (G-CSF) or growth factors at the time of initiation of study drug

History of allergic reactions attributed to compounds of similar chemical or biologic composition to CRLX101 and camptothecins

Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01612546